PhysioNet, established in 1999 as the NIH-sponsored Research Resource for Complex Physiologic Signals, has attained a preeminent status among biomedical data and software resources. Its data archive, PhysioBank, was the first, and remains the world's largest, most comprehensive and widely used repository of time-varying physiologic signals. PhysioToolkit, its software collection, supports exploration and quantitative analyses of PhysioBank and similar data with a wide range of well-documented, rigorously tested open-source software that can be run on any platform. PhysioNet's team of researchers leverages results of other funded projects to drive the creation and enrichment of: i) Data collections that provide increasingly comprehensive, multifaceted views of pathophysiology over long time intervals, such as the MIMIC III (Medical Information Mart for Intensive Care) Database of critical care patients; ii) Analytic methods that lead to more timely and accurate diagnoses of major public health problems (such as life-threatening cardiac arrhythmias, infant apneas, fall risk in older individuals and those with neurologic disease, and seizures), and iii) Elucidation of dynamical changes associated with a variety of pathophysiologic processes and aging (such as cardiopulmonary interactions during sleep disordered breathing syndromes); User interfaces, reference materials and services that add value and improve accessibility to PhysioNet's data and software (such as PhysioNetWorks, a virtual laboratory for data sharing). Impact: Cited in The White House Fact Sheet on Big Data Across the Federal Government (March 29, 2012), PhysioNet is a proven enabler and accelerator of innovative research by investigators with a diverse range of interests, working on projects made possible by data that are inaccessible otherwise. The creation and development of PhysioNet were recognized with the 2016 highest honor of the Association for the Advancement of Medical Instrumentation (AAMI). PhysioNet's world- wide, growing community of researchers, clinicians, educators, students, and medical instrument and software developers, retrieve about 380 GB of data per day. By providing free access to its unique and wide-ranging data and software collections, PhysioNet is invaluable to studies that currently result in an impressive average of nearly 250 new scholarly articles per month by academic, clinical, and industry-affiliated researchers worldwide. Over the next year we aim to sustain and enhance PhysioNet's impact with new technology and data; and complete the 2019 PhysioNet/Computing in Cardiology Challenge on sepsis.